NLRP3 inflammasome-dependent pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice

Li, Dongxia; Wang, Chang-Nan; Wang, Yan; Ye, Chang-Lin; Jiang, Lai; Zhu, Xiaoyan; Liu, Yujian

doi:10.1016/j.bbr.2020.112684

Cited by 43 publications

(34 citation statements)

References 50 publications

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“…Damage to the DNA of HEK-293 cells was analyzed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Cells were stimulated with lead for 24 h after pretreatment with SGF and DMSA for 1 h. Then, they were fixed in 4% paraformaldehyde in phosphate-buffered saline (PBS) and processed for TUNEL staining using the One Step TUNEL Apoptosis Assay Kit (Yeasen Biotechnology, Shanghai, China) as described previously ( Li et al., 2020 ). Proteinase K was used to permeabilize cells according to manufacturer instructions.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Shi

Tian

et al. 2020

Front. Pharmacol.

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Lead (Pb) is an important environmental pollutant. Oxidative stress and the inflammatory response have been postulated as mechanisms involved in lead-induced renal damage. Smilax glabra Roxb. has been used for treatment of heavy-metal poisoning in China for 500 years. We investigated S. glabra flavonoids extract (SGF) could attenuate lead acetate-induced nephrotoxicity in weaning rats and human embryonic kidney (HEK)-293 cells, and investigated the possible mechanisms. Compared with Pb exposed group of weaning rats, SGF could significantly promote lead excretion in the blood and kidney, and increase the content of the renal-function indicators blood urea nitrogen, serum uric acid, and serum creatinine. SGF could improve the glomerular filtration rate (GFR) and histologic changes in the kidneys of weaning rats exposed to Pb. SGF could also reduce lead-induced cytotoxicity, improve DNA damage-induced apoptosis and cleaved caspase-3-mediated apoptosis in HEK-293 cells stimulated with Pb. SGF significantly increased the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase, and decreased excessive release of reactive oxygen species (ROS) and malondialdehyde in the kidneys of the weaning rats and in HEK-293 cells. The antioxidant mechanism of SGF related to activation of the Kelch-like ECH-associated protein 1/nuclear-factor-E2-related factor 2/hemeoxygenase-1(Keap1/Nrf2/HO-1) pathway. SGF could inhibit secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α induced by Pb in vivo and in vitro . The anti-inflammatory mechanism of SGF related to inhibition of ROS and pro-inflammatory cytokines triggered the nuclear factor-kappa B (NF-κB) pathway through blockade of inhibitors of I-κB degradation, phosphorylation of NF-κB p65, and nuclear translocation of p65. Our findings indicate that SGF could be a natural antioxidant and anti-inflammatory agent for treating lead-induced nephrotoxicity.

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Section: Methodsmentioning

confidence: 99%

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Shi

Tian

et al. 2020

Front. Pharmacol.

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“…Additionally, the association between glutamate and in ammation has been well demonstrated [35], as a large number of clinical studies suggest that pathophysiology of depression is associated with dysfunction of the predominant glutamatergic system, known as the glutamate hypothesis [51]. The NLRP3 in ammasome also is responsible for pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice [52]. Therefore, the increased number of dark neurons are associated with enhanced activation of NF-κB/ NLRP3 in ammasome pathway.…”

Section: Discussionmentioning

confidence: 98%

Intraventricular T3 Reverses Chronic Restraint Stress-Induced Depressive-Like Behaviors: Inhibition of NF-κB/ NLRP3 Inflammasome Pathway in the Hippocampus

Mokhtari

El-Kenawy

2021

Preprint

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In this study, the effects of triiodothyronine (T3) were evaluated on the NLRP3 inflammasome complex formation in the hippocampus of the rat with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to the following groups: Control, Model, and Model + T3. In Model or Model + T3 group, a single dose of PBS or T3 () was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal NF-κB, NLRP3, ASC, and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were seen in the T3 group compared to the Model group (P < 0.05). Also, the Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings of confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.

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“…A large number of clinical studies suggest that the pathophysiology of depression is associated with dysfunction of the predominant glutamatergic system, known as the glutamate hypothesis [51]. The NLRP3 in ammasome also is responsible for pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice [52]. Therefore, the increased number of dark neurons is associated with the activation of the NF-κB/ NLRP3 in ammasome pathway.…”

Section: Discussionmentioning

confidence: 99%

Intraventricular T3 reverses chronic restraint stress-induced depressive-like behaviors: Inhibition of NF-κB/ NLRP3 inflammasome pathway in the hippocampus

Mokhtari

El-Kenawy

2021

Preprint

View full text Add to dashboard Cite

In this study, the effects of triiodothyronine (T3) were evaluated on the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex formation in the rat's hippocampus with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to following groups: Control, Model, and Model + T3. In the Model or Model+T3 group, a single dose of PBS or T3 was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate the depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal nuclear factor kappa B (NF-κB), NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were observed in the T3 group compared to the Model group (P < 0.05). The Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.

show abstract

NLRP3 inflammasome-dependent pyroptosis and apoptosis in hippocampus neurons mediates depressive-like behavior in diabetic mice

Cited by 43 publications

References 50 publications

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Intraventricular T3 Reverses Chronic Restraint Stress-Induced Depressive-Like Behaviors: Inhibition of NF-κB/ NLRP3 Inflammasome Pathway in the Hippocampus

Intraventricular T3 reverses chronic restraint stress-induced depressive-like behaviors: Inhibition of NF-κB/ NLRP3 inflammasome pathway in the hippocampus

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